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Biomedical subjects

J Chorostowska-Wynimko

Publications and source records attributed to J Chorostowska-Wynimko.

At least 19 recordsLinked to original sources
PubMed2006

Vascular-endothelial growth factor (VEGF) in patients with peripheral ischemia.

Vascular endothelial growth factor (VEGF) is a key cytokine responsible for the spontaneous new blood vessel formation in the course of peripheral ischemia. It has repeatedly been observed in patients with critical leg ischemia that their clinical status does not reflect any effective local neovascularization processes as well as VEGF system up-regulation. Therefore, the aim of present study was to compare the proangiogenic status, assessed as the serum VEGF concentration, in patients with mild, moderate, and severe peripheral ischemia and to analyze to what extend it is influenced by the therapy applied. Serum VEGF level was evaluated by ELISA method in 31 patients with peripheral ischemia at different time points throughout the treatment. On Day 0 (before treatment), Day 2, and Day 7, VEGF concentration was significantly higher in subjects with critical leg ischemia (Group I) than in other groups (P<0.001). In Group I, VEGF decline was reported on Day 30 following radical surgery, while in a group of moderate disease treated by revascularization surgery a significant increase in serum VEGF concentration was observed (Day 7 and Day 30) (P=0.02). Serum cytokine level in the patients with mild ischemia (Group III) on pharmacotherapy was stable throughout the observation period. Interestingly, the increase in VEGF levels throughout the study period from Day 0 to Day 30 was significantly greater in unsuccessfully treated patients compared with subjects who positively responded to therapy or did not show any response at all. We conclude that mechanisms other than hypoxia might drive the observed up-regulation of VEGF production in peripheral ischemia.

Blood Cell Count↗
PubMed2006

Inflammatory markers in the exhaled breath condensate of patients with pulmonary sarcoidosis.

Pulmonary sarcoidosis may progress to fibrosis in some patients, so that close monitoring of its activity is essential for recommending clinical strategy. Examination of airway inflammatory markers in bronchoalveolar lavage (BAL) is one of the methods applied to assess the disease severity. Recently, the expired breath condensate (EBC) has become another source of cytokines and mediators. In sarcoidosis, except for NO and oxidative stress markers, no other mediators have yet been estimated in the exhaled air. In the present study we attempted to answer the question of whether airway inflammatory markers in pulmonary sarcoidosis patients might be assessable in EBC and to what extend these markers might reflect the disease activity in the lungs IL-6, TNF-alpha, PAI-1, and IGF-1 were measured by Elisa method in EBC and BALF samples from 9 patients with newly-diagnosed pulmonary sarcoidosis. TNF-alpha, IGF-1, and PAI-1 levels in EBC and BAL samples were comparable and closely positively correlated [TNF-alpha (r=0.79, P<0.001), IGF-1 (r=0.94, P<0.001), and PAI-1 (r=0.81, P<0.001)]. In contrast, IL-6 concentration in EBC was significantly lower compared with that in BALF, while the correlation between both materials was negative (r=-0.47, P<0.05). An important distinction in IL-6 performance, which might explain this inconsistency, is its tendency to form more complex molecular forms of a higher weight than that of other cytokines. Our study shows that EBC reflects cytokine production in the lung as effectively as BALF, providing that the characteristics of proteins evaluated allow their easy transfer into the exhaled air. Further studies are required before accepting EBC samples as an equivalent to BALF.

Adult↗
PubMed2005

In vitro angiomodulatory activity of sera from type 2 diabetic patients with background retinopathy.

Diabetic retinopathy is the leading cause of adult vision loss and blindness. The most important contributors to the development of diabetic retinopathy are hyperglycemia and hypoxemia that lead to increased vasopermeability, endothelial cell proliferation, and pathological neovascularization. In our previous studies, close relationship between proangiogenic activity of sera from type 2 diabetes mellitus patients (DM2) with background retinopathy, assessed in the in vivo serum-induced mouse cutaneous test (SIA), and VEGF and IL-18 serum concentration were observed. Moreover, it was clearly shown that IGF-1 might play an important role in the negative regulation of neoangiogenesis induced by DM2 patients' sera by diminishing the VEGF stimulatory effect. To confirm the observed phenomenon we evaluated the effect of DM2 patients' sera on the in vitro proliferative activity of human endothelial cells, which is critical for the sprouting and generation of new blood capillaries. Endothelial proliferative activity was significantly higher in the presence of sera from DM2 patients than from healthy controls (P<0.001), as estimated by the MTT test. Moreover, the examined sera from DM2 patients were characterized by increased IL-18 (P<0.05), diminished IGF-1 (P<0.02), and unchanged VEGF levels compared with those in controls. In conclusion, the present study showed a strong stimulatory effect of DM2 patients' sera on the proliferation of endothelial cells, which, along with the findings of our previous studies, proves that the described phenomenon is universal and valid for both animal and human endothelium.

Aged↗
PubMed2005

Disturbed angiogenic activity in sera from obstructive sleep apnea patients.

It is increasingly recognized that obstructive sleep apnea (OSA) syndrome is a systematic rather than local disorder. There is also growing evidence that apart from the syndrome's major features: intermittent hypoxia and sleep fragmentation, functional activity of the immune system is altered in OSA patients, with several cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) taking active part in sleep regulation. Little is known about the effects exerted by chronic intermittent hypoxia combined with persistent pro-inflammatory activity of the immune system on the vascular micro milieu in OSA. In this study we attempted to confirm the hypothesized imbalance between pro- and anti-angiogenic factors by evaluating direct and indirect angiogenic activity of OSA patients' sera in the in vivo serum-induced angiogenesis (SIA) and leukocyte-induced (LIA) assays, respectively, in mice. Both tests revealed significantly inhibited angiogenic activity of OSA patients' sera compared with healthy controls (P<0.001). Moreover, differences related to the subject's weight regarding in the mean number of newly-formed vessels were observed with a significantly greater inhibition in the normal-weighing apneic subjects than in the overweight or obese ones (P<0.01). The angiogenesis inhibition index was positively related to the serum IL-6 level (r=0.35; P<0.05) in the OSA group, but not to TNF-alpha, fasting serum leptin, or OSA syndrome severity as assessed by the AHI index. Our results demonstrate that OSA is accompanied by disturbed serum angiogenic activity, apparently resulting from an imbalance between pro- and anti-angiogenic factors, some of them being produced by the adipose tissue. The disordered angiogenic activity might be related to the pathophysiology of OSA and should be considered an important causative factor for the increased prevalence of cardiovascular diseases in OSA patients.

Adipose Tissue↗
PubMed2004

Multiple effects of theobromine on fetus development and postnatal status of the immune system.

Caffeine and its active derivative, theobromine, are probably the most frequently ingested pharmacologically active substances. Considering their uninhibited transport via the placental barrier as well as immature enzymatic activities and metabolic pathways in embryos and infants resulting in the longer half-life of methyloxanthines and their accumulation, unrestrained uptake of these substances might result in noticeably more pronounced biological effects during pregnancy and the postnatal period. Our previous studies have shown that methyloxanthines are significant inhibitors of angiogenic growth factors production and angiogenesis itself. We have hypothesized that increased uptake of these substances might affect embryonal angiogenesis and, later in the postnatal period, maturation and functional activity of the offspring's immune system. The study was performed on 2-month-old Balb/c mice fed theobromine 2 or 6 mg/day during pregnancy and lactation. On day 18 of pregnancy the number and weight of embryos were assessed as was their tissue angiogenic activity, using the cutaneous angiogenesis assay. In the group of 4-week-old sucklings, body and spleen were weighed together with the trunk, and tail and limb length were measured. Six weeks after birth the splenocytes' mitogen-induced activity and their ability to induce graft-versus-host reaction as well as the humoral response to SRBC antigen were evaluated. Content of theobromine in the embryos' tissue was estimated by high liquid performance chromatography (HPLC). Theobromine feeding resulted in significant inhibition of embryo growth as assessed by their weight and decreased angiogenic activity of their tissue. The theobromine content in embryo tissue from treated groups was higher than in the controls, and the difference was close to significant. In the postnatal period the discrepancies in the treated 4-week-old group's development were also observed in the significantly shorter limbs in comparison to the controls. Moreover in the treated group of 6-week-old sucklings, considerable variations in the immune system's functional activity were registered as far as cellular and immune response were concerned. Respectively, the splenocytes' mitogen-induced proliferative activity was significantly suppressed while the graft-versus-host reaction was up-regulated, and the serum antibodies titer was elevated in correspondence to the observed spleen enlargement. We concluded that a theobromine-enriched diet affects progeny development in both prenatal and postnatal periods. Consequently, particular attention should be paid to the reduction of theobromine consumption, and most probably that of other methyloxanthines, during pregnancy and lactation.

Angiogenesis Inhibitors↗
PubMed2004

Cellular components of the bronchoalveolar lavage correlate with lung function impairment and extrapulmonary involvement markers in active sarcoidosis.

Sarcoidosis is a chronic inflammatory multiorgan disease of unknown origin. Our previous study demonstrated a significant correlation between the relative count of non CD4(+), non CD8(+) lymphocytes in bronchoalveolar lavage of active sarcoidosis patients and proangiogenic activity of BAL homogenates. The aim of the present study was to evaluate in a group of 40 patients with active sarcoidosis the possible relationship between the intensity of alveolitis, particularly the non CD4(+), non CD8(+) lymphocyte subset, and other parameters characterizing the level of pulmonary (lung function tests) and extrapulmonary (spleen longitudinal dimension) disease activity. We found that the relative count of non CD4(+), non CD8(+) lymphocytes in BAL correlated positively with spleen size (r=0.50, P<0.01) and negatively with static compliance (r=0.43, P<0.05). We concluded that the lymphocytes belonging to the non CD4(+)non CD8(+) subset participate in the inflammatory process in sarcoidosis. However, more detailed phenotypic and functional characteristics of this cellular population are needed.

Adult↗
PubMed2004

Plasminogen activator inhibitor type-1 controls the process of the in vitro sprout formation.

Plasminogen activator inhibitor type-1 (PAI-1), the primary regulator of plasminogen activator - urokinase (uPA) plays a crucial role in the cell adhesion and migration and in angiogenesis. We had previously demonstrated that PAI-1 - endothelial cell interplay is critical for the formation of new blood vessels and the process is mostly conducted via uPA- anti-proteinase interaction. In the present study we wished to further examine the role of PAI-1 in the sprout formation, representing the first step of new capillary vessels development by evaluating the effect of PAI-1 on the sprout area. We addressed the issue by assessing the influence of cysteine-mutated PAI-1 proteins characterized by a prolonged half-life time (hD beta T - T(1/2)= 63.59 h and beta T-T(1/2)= 6931.47 h), and therefore more stable anti-uPA activity, on the appearance of newly formed sprouts. We found that both CysPAI-1 proteins significantly diminished the mean sprout area in a concentration-dependent fashion. The inhibitory effect present in the two examined endothelial cells systems of different origin and functional characteristics - human umbilical vein endothelial cells (HUVEC) and human lung microvascular endothelial cells (HLMVEC) cultures - was noticeably greater for HLMVEC -high urokinase-producers. Moreover, the inhibition rate was significantly greater for the beta T mutant than that for the hD beta T PAI-1 mutant in all examined doses (P<0.002), proving a key role of anti-proteinase activity for this effect. We concluded that, apart from the total sprout length, as it had repeatedly been demonstrated before, also affects the sprout area in the in vitro sprout formation angiogenesis assay. This effect was achieved mainly via PAI-1's antiproteinase activity.

Cells, Cultured↗
PubMed2003

Inhibitory effect of Greenland shark liver oil combined with squalen and arctic birch ashes on angiogenesis and L-1 sarcoma growth in Balb/c mice.

Sharks have been claimed to be resistant to cancer and oil from their livers have been used in Scandinavian folk medicine as anti-tumor drug. Shark liver oil contains 40% or more of squalene. Fish liver oil is also rich in squalene and polyunsaturated n-3 fatty acids. The aim of this work was to determine the anti-angiogenic and anti-tumor effects of these substances, together with another Scandinavian traditional remedy--arctic birch ashes--in Balb/c mice after transplantation of syngeneic L-1 sarcoma. All substances tested, alone or in combinations, significantly diminished cutaneous angiogenesis induced by tumor cells, and tumor growth.

Animals↗
PubMed2003

Chocolate feeding of pregnant mice influences length of limbs of their progeny.

UNLABELLED: We previously reported the inhibitory effect of various methyloxantines and phenolic compounds on tumor-induced angiogenesis and the production of angiogenic growth factors. The aim of the present work was to evaluate the effect of chocolate (CH), food containing substantial amounts of methyloxantine theobromine and polyphenols (mainly catechins), given to mice during pregnancy and the lactation period, on weight of organs, length of limbs, and bone vascular endothelial growth factor (VEGF) concentration (tested by ELISA), in 4-week old offspring. The study was performed on 2-month old Balb/c mice fed during pregnancy and lactation 400 mg of CH daily. Content of polyphenols (catechines) and theobromine in the chocolate was estimated by high liquid perforance chromatography (HPLC). Concentration of VEGF was tested by ELISA. Feeding pregnant mice chocolate produced the following effects: decrease of relative length of limbs and thigh bones in 4-week old progeny and decrease in VEGF content of offspring femoral bones. CONCLUSION: attention should be paid to possible unwanted effects of catechine- and methyloxantine-rich food and beverages during pregnancy and lactation. 200 mg of chocolate per mouse corresponds to 100 g per person.

Administration, Oral↗
PubMed2001

The synergistic effect of lactic acid bacteria and alkylglycerols on humoral immunity in mice.

Investigations on immune suppression and reconstitution of immune functions dependent on the presence of physiological microflora allow us to conclude that symbiotic microorganisms such as Lactobacillus sp. are essential for adequate activity of the defense system in humans. In addition to their beneficial influence on the intestinal microbial balance, these microorganisms exert a variety of immunomodulatory effects on the host immune system. On the other hand, immunostimulatory animal-derived substances rich in alkylglycerols have been shown to enhance lactic acid bacteria proliferation. Therefore, the aim of the present study was to evaluate the effects on murine humoral response of the combined administration of lyophilized combination of three lactic acid bacteria: L. acidophilus, L. bulgaricus and Bifidobacterium bifidum together with alkylglycerol-rich shark liver oil. The lactic acid bacteria mixture induced markedly stronger enhancement of the humoral response than alkylglycerols did. A significant synergistic stimulatory effect of lactic acid bacteria and alkylglycerols was observed in both treatment schedules: post- as well as in preimmunization with sheep red blood cells. However, their concomitant administration exerted stronger immunomodulatory effect than did the alternative route of treatment.

Animals↗
PubMed2000

[Influence of isoniazid on selected parameters of immunological response].

Isoniazid (INH), antituberculous drug with immunomodulatory properties, have been described as lupus-like syndrome inducer. The development of autoimmunological phenomena results from immunoregulatory disturbances. The goal of this work was to determine the influence of INH on selected parameters of the immune response in vivo and in vitro. In vivo (in B6AF1 mice) the influence of long-term treatment on primary humoral response and cellular response was evaluated. Drug dose was 25 mg/kg. In vitro (using peripheral blood of volunteers) the influence of INH on mitogen induced proliferation, metabolic activity of granulocytes and production of angiogenic cytokines by diverse subpopulation of mononuclear cells was examined. The concentrations tested were 0.5 mg/ml, 5 mg/ml and 50 mg/ml. No effect of INH could be demonstrated on the production anti-SRBC antibodies nor on the cellular response in mice. In vitro INH added to the cell cultures increased PHA and ConA stimulated proliferation. The chemiluminescence of human granulocytes increased in the presence of INH. Drug enhanced production of angiogenic cytokines by human lymphocytes CD4+ and suppressed angiogenic activity of CD8+ cells. The results suggest that INH has strong immunomodulatory properties which may explain its involvement in pathogenesis of lupus-like disease.

Animals↗
PubMed2000

[Theophylline--contemporary views on cellular mechanism of action].

Theophylline has been used in the treatment of obstructive pulmonary diseases since 30s. However, its mechanism of action is still poorly defined. Up to now, its several different actions on the cellular levels are known or hypothesised including most important--inhibition of phosphodiesterase isoenzymes and antagonism of adenosine, as well as enhancement of catecholamine secretion and modulation of calcium ions fluxes. Author reviews all of the proposed theories, outlining existing arguments for and against.

Adenosine↗
PubMed1998

[The influence of rifampicin on selected parameters of immunologic response].

Rifampicin (RMP), antituberculous drug, has been controversially described for many years as an immunosuppressant. The goal of this work was to determine the influence of RMP on selected parameters of the immune response in vivo and in vitro. In vivo (in B6AF1 mice) the influence of long-term treatment on primary humoral response and cellular response was evaluated. Drug dose was 50 mg/kg. In vitro (using peripheral blood of volunteers) the influence of RMP on mitogen induced proliferation, metabolic activity of granulocytes and leukocyte induced angiogenesis by diverse subpopulation of mononuclear cells was examined. The concentrations tested were 7 and 70 micrograms/ml. RMP slightly stimulated production of anti-SRBC antibodies and suppressed cellular response in mice, decreased PHA and ConA induced proliferation in higher concentration and strongly inhibited chemiluminescence at concentration used. RMP inhibited also leukocytes induced angiogenesis.

Animals↗
PubMed1997

Screening of angiogenesis inhibitors by modified tumor-induced angiogenesis (TIA) test in lung cancer.

Aberrant angiogenesis-the new vessels formation is a mandatory event in the process of tumor growth and expansion. Studies on mechanisms involved in tumor-induced angiogenesis (TIA) and on its possible inhibitors are needed in order to introduce in future new methods of tumor treatment. The aim of our study was to determine the usefulness of the modified cutaneous TIA (mice without immunosuppression) test for screening in vivo of the angiogenesis modifiers. In both models (classical and modified TIA) we demonstrated comparable angiogenesis activity following human lung cells inoculation and similar degree of neovascularization response inhibition caused by theobromine. We reported that in modified TIA model preincubation with theobromine significantly suppressed angiogenic potential of human lung cancer cells as well as the ability of those cells to produce proangiogenic cytokine-bFGF.

Adenocarcinoma↗
PubMed1997

[Immunomodulatory properties of therapeutic and subtherapeutic levels of theophylline: effect on metabolic activity of human monocytes].

The aim of present study was to analyze the potential immunomodulatory effects of theophylline. We studied the influence of therapeutic and subtherapeutic drug concentrations on the metabolic human monocytes activity using the chemiluminescence test, that allows to evaluate the production of free oxygen radicals. Subtherapeutic theophylline concentrations of 2.5 and 5 micrograms/ml significantly increased monocytes spontaneous chemiluminescence activity. Moreover, in concentrations 5-20 micrograms/ml theophylline interfered with the process of monocyte activation by zymosan: decreasing O2-total and maximal production as well as affecting duration of the "respiratory burst" reaction. Correlation between theophylline concentration and intensity of its suppressive effect was also observed. Therefore we concluded that theophylline might be useful in the treatment of allergic inflammation characterising bronchial asthma.

Adjuvants, Immunologic↗
PubMed1997

[Theophylline does not exert an effect on the early phase of TNF-alpha through the activity of human monocytes].

Tumor necrosis factor-alpha (TNF-alpha) is commonly recognized as a one of the most important mediators of allergic inflammation and hyperreactivity in bronchial asthma. Several studies proved the inhibitory effect of theophylline (including it's subtherapeutic doses) on the synthesis of TNF-alpha in 24 hrs monocyte cultures. The aim of our study was to determine the influence of therapeutic and subtherapeutic concentrations of the drug on the early phase of TNF-alpha release. We showed that theophylline did not significantly alter the cytokine concentration measured by Elisa method in supernatants from 2 hrs monocyte cultures stimulated by LPS (1 microgram/ml). Therefore, we concluded that the mechanism of theophylline inhibitory action on TNF-alpha production is more likely associated with changes in genome expression, than with the inhibition of the cytokine liberation from the cell.

Humans↗